EFFECTS OF MU-OPIOID AGONISTS ALONE AND IN COMBINATION WITH COCAINE AND D-AMPHETAMINE IN RHESUS-MONKEYS TRAINED TO DISCRIMINATE COCAINE

Psychomotor stimulants and mu opioid agonists ave often used together by polydrug abusers, and it has been suggested that this form of polyd rug abuse may result from the ability of stimulants and mu agonists to enhance each other's abuse-related effects. To investigate this possi bility, the present study examined stimulant-opioid interactions in rh esus monkeys trained to discriminate cocaine. Specifically, the effect s of the mu opioid agonists heroin, alfentanil, fentanyl, and morphine administered alone ol ill combination with cocaine or d-amphetamine w ere examined in Jive monkeys trained to discriminate 0.4 mg/kg cocaine (IM) from saline in a two-level, food-reinforced drug discrimination procedure. When administered alone, the vapid onset mu agonists heroin (0.032-0.32 mg/kg) and alfentanil (0.01-0.1 mg/kg) substituted comple tely for cocaine in three of five monkeys but produced primarily salin e-appropriate responding in the other two monkeys. The slower onset mu agonists fentanyl (0.0056-0.056 mg/kg) and morphine (0.56-10 mg/kg) s ubstituted for cocaine in only one of five monkeys. When administered as pretreatments to cocaine, morphine and fentanyl increased levels of cocaine-appropriate responding produced by low doses of cocaine in so me monkeys. Morphine pretreatment also increased levels of cocaine-app ropriate responding produced by low doses of amphetamine in some monke ys. However, in other monkeys, morphine and fentanyl pretreatment did not alter the discriminative stimulus effects of cocaine of amphetamin e. These results indicate that there are substantial individual differ ence in the effect of mu agonists in cocaine-discriminating rhesus mon keys. In some monkeys, mu agonists mimic or enhance the discriminative stimulus of cocaine, whereas in other monkeys, mu agonists neither mi mic nor enhance the effects of stimulants.